The successful development of animal models of inherited human diseases generally requires a multidisciplinary approach, involving clinicians, geneticists, biochemists, veterinary pathologists, human pathologists and other specialists. The study of disease mechanisms naturally encompasses many disciplines and thus, the pathology laboratory provides some of the more essential services in support of these common goals. The specific aims of the Pathology Core in this Program Project are to: (i) Provide gross and microscopic pathology support as needed for all of the projects described in the Program Project. These activities will provide information of crucial importance in analysis of gene targeted organs/systems and for evaluation of unexpected deaths due to developmental or other defects. (ii) Provide a wide range of specialized pathology methods such as in situ hybridization (ISH), immunofluorescence (IFA), immunohistochemistry, ultrastructural studies, hematologic analyses and others, which will be required by most of the projects in this Program Project at some stage in development and analysis of their models. These services will be provided by certified veterinary pathologists (ACVP) and a well qualified research assistant (HT, HTL-ASCP), with the advice and consultation of selected consultants as needed in the establishment or development of additional new procedures. The Animal Diagnostic/Health Surveillance Laboratory in the Department of Comparative Medicine of the University of Alabama at Birmingham has more than twenty- five years of experience in animal model development and in provision of many of the services of this Pathology Core.